POS0826 SAFETY PROFILE OF UPADACITINIB UP TO 6.5 YEARS OF EXPOSURE IN PATIENTS WITH RHEUMATOID ARTHRITIS
Authors: S. B. Cohen, R. Van Vollenhoven, J. Curtis, L. Calabrese, C. Zerbini, Y. Tanaka, L. Bessette, C. Richez, S. Strengholt, D. Coombs, N. Khan, A. Gara, G. R. Burmester
Journal: Annals of the Rheumatic Diseases (2023)

<h3>Background</h3> Upadacitinib (UPA) is an oral JAK inhibitor that has demonstrated safety and efficacy in patients (pts) with moderate-to-severe active RA in the phase 3 SELECT clinical program.<sup>[1–6]</sup> <h3>Objectives</h3> To describe the long-term integrated safety profile of UPA relative to active comparators in pts with RA from the SELECT clinical program through the cutoff date of 15 August 2022. <h3>Methods</h3> Pooled safety data were analyzed from 6 randomized controlled trials evaluating UPA in RA.<sup>[1–6]</sup> Treatment-emergent adverse events (TEAEs) and AEs of special interest were summarized for the following groups: pooled UPA 15 mg once daily (QD; UPA15, 6 trials), MTX (1 trial), and adalimumab (ADA) 40 mg every other week (EOW; 1 trial). TEAEs were defined as AEs with an onset after the first dose and ≤ 30 days (UPA and MTX) or ≤ 70 days (ADA) after the last dose of study drug and reported as exposure-adjusted event rates (EAERs) per 100 patient-years (PY; E/100 PY). The standardized mortality ratio (SMR) was estimated for the general population using World Health Organization country-age-gender specific mortality rates through 2016. <h3>Results</h3> 3209 pts received ≥ 1 dose of UPA15 with 10 782.7 PY of exposure. EAERs of AEs, serious AEs (SAEs), and AEs leading to discontinuation on UPA15 were comparable to MTX and ADA (<b>Table 1</b>). COVID-19 pneumonia was the most common SAE with UPA15 (0.7 E/100 PY). Rates of serious infections were similar between UPA15 and ADA but higher compared with MTX (<b>Figure 1</b>). Herpes zoster (HZ) rates were higher with UPA15 vs MTX and ADA. Most HZ cases with UPA15 were non-serious (95%) and affected a single dermatome (75%) or unilateral multiple dermatomes (16%); 8% of cases were reported as disseminated and none involved the central nervous system. Creatine phosphokinase elevations were transient and more common with UPA15 than MTX or ADA. Anemia and neutropenia rates were similar between UPA15 and ADA. Most hepatic disorders were mild or moderate transaminase elevations. Treatment discontinuation due to these lab events was rare (≤ 0.1 E/100 PY). Similar rates of adjudicated MACE, adjudicated VTE, and malignancy (excluding non-melanoma skin cancer [NMSC]) were observed across treatment groups. The rate of NMSC was numerically higher with UPA15 vs ADA; no cases occurred with MTX. SMR analysis indicated that the mortality rate among pts with RA treated with UPA15 was not higher than what would be expected among the general population (SMR [95% CI]: 0.67 [0.52, 0.86] including COVID-19 deaths; 0.41 [0.29, 0.56] excluding COVID-19 deaths). <h3>Conclusion</h3> The integrated safety profile of UPA in pts with RA remained consistent with previous findings,<sup>[7]</sup> with no new safety risks identified up to 6.5 years of exposure. Similar rates of AEs of special interest were observed for UPA15 and ADA, except for higher rates of HZ, CPK elevations, and NMSC with UPA. <h3>References</h3> [1]Burmester GR, et al. <i>Lancet</i>. 2018;391:2503–12. [2]Smolen JS, et al. <i>Lancet</i>. 2019;393:2303–11. [3]Fleischmann R, et al. <i>Arthritis Rheumatol</i>. 2019;71:1788–1800. [4]Genovese MC, et al. <i>Lancet</i>. 2018;391:2513–24. [5]van Vollenhoven R, et al. <i>Arthritis Rheumatol</i>. 2020;72:1607–20. [6]Rubbert-Roth A, et al. <i>N Engl J Med</i>. 2020;383:1511–21. [7]Cohen SB, et al. <i>Ann Rheum Dis</i> 2020;79:319–20. <h3>Acknowledgements</h3> AbbVie funded this study and participated in the study design, research, analysis, data collection, interpretation of data, review, and approval of the abstract. All authors had access to relevant data and participated in the drafting, review, and approval of this publication. No honoraria or payments were made for authorship. Medical writing support was provided by Julia Zolotarjova, MSc, MWC, of AbbVie. <h3>Disclosure of Interests</h3> Stanley B. Cohen Consultant of: AbbVie, Amgen, Boehringer Ingelheim, Eli Lilly, Gilead, Pfizer, Roche, and Sandoz, Grant/research support from: AbbVie, Amgen, Boehringer Ingelheim, Eli Lilly, Gilead, Pfizer, Roche, and Sandoz, Ronald van Vollenhoven Speakers bureau: AbbVie, AstraZeneca, Biogen, BMS, Galapagos, GSK, Janssen, MSD, Novartis, Pfizer, Roche, Sanofi, and UCB, Consultant of: AbbVie, AstraZeneca, Biogen, BMS, Galapagos, GSK, Janssen, MSD, Novartis, Pfizer, Roche, Sanofi, and UCB, Grant/research support from: AbbVie, AstraZeneca, Biogen, BMS, Galapagos, GSK, Janssen, MSD, Novartis, Pfizer, Roche, Sanofi, and UCB, Jeffrey Curtis Consultant of: AbbVie, Amgen, BMS, CorEvitas, Eli Lilly, Janssen, Pfizer, Sanofi, and UCB, Grant/research support from: AbbVie, Amgen, BMS, CorEvitas, Eli Lilly, Janssen, Pfizer, Sanofi, and UCB, Leonard Calabrese Speakers bureau: AbbVie, BMS, Crescendo, Genentech, Gilead, GSK, Horizon, Janssen, Novartis, and Sanofi, Consultant of: AbbVie, BMS, Crescendo, Genentech, Gilead, GSK, Horizon, Janssen, Novartis, and Sanofi, Cristiano Zerbini Speakers bureau: Amgen, Eli Lilly, GSK, MSD, Novartis, Pfizer, Roche, Sanofi, Consultant of: Amgen, Eli Lilly, GSK, MSD, Novartis, Pfizer, Roche, Sanofi, Grant/research support from: Amgen, Eli Lilly, GSK, MSD, Novartis, Pfizer, Roche, Sanofi, Yoshiya Tanaka Speakers bureau: AbbVie, Amgen, Asahi-Kasei, Astellas, AstraZeneca, Boehringer-Ingelheim, BMS, Chugai, Corrona, Daiichi-Sankyo, Eisai, Eli Lilly, Gilead, Kowa, Mitsubishi-Tanabe, Takeda, YL Biologics, and Takeda, Consultant of: AbbVie, Amgen, Asahi-Kasei, Astellas, AstraZeneca, Boehringer-Ingelheim, BMS, Chugai, Corrona, Daiichi-Sankyo, Eisai, Eli Lilly, Gilead, Kowa, Mitsubishi-Tanabe, Takeda, YL Biologics, and Takeda, Grant/research support from: AbbVie, Amgen, Asahi-Kasei, Astellas, AstraZeneca, Boehringer-Ingelheim, BMS, Chugai, Corrona, Daiichi-Sankyo, Eisai, Eli Lilly, Gilead, Kowa, Mitsubishi-Tanabe, Takeda, YL Biologics, and Takeda, Louis Bessette Speakers bureau: AbbVie, Amgen, BMS, Celgene, Eli Lilly, Gilead, Janssen, MSD, Novartis, Pfizer, Roche, Sanofi, Organon, TEVA, and UCB, Consultant of: AbbVie, Amgen, BMS, Celgene, Eli Lilly, Gilead, Janssen, MSD, Novartis, Pfizer, Roche, Sanofi, Organon, TEVA, and UCB, Grant/research support from: AbbVie, Amgen, BMS, Celgene, Eli Lilly, Gilead, Janssen, MSD, Novartis, Pfizer, Roche, Sanofi, Organon, TEVA, and UCB, Christophe Richez Speakers bureau: Amgen, AstraZeneca, Biogen, BMS, Eli Lilly, Galapagos, GSK, Hospira, Mylan, Novartis, Pfizer, Roche, and Sandoz, Consultant of: Amgen, AstraZeneca, Biogen, BMS, Eli Lilly, Galapagos, GSK, Hospira, Mylan, Novartis, Pfizer, Roche, and Sandoz, sander strengholt Shareholder of: AbbVie, Employee of: AbbVie, Derek Coombs Shareholder of: AbbVie, Employee of: AbbVie, Nasser Khan Shareholder of: AbbVie, Employee of: AbbVie, Andrew Gara Shareholder of: AbbVie, Employee of: AbbVie, Gerd Rüdiger Burmester Speakers bureau: AbbVie, Amgen, Eli Lilly, Galapagos, Gilead, Janssen, MSD, Pfizer, Roche, and UCB, Consultant of: AbbVie, Amgen, Eli Lilly, Galapagos, Gilead, Janssen, MSD, Pfizer, Roche, and UCB.